Differences In Coagulation Parameters Research Articles

An Evaluation of Hemostatic Dysregulation in Canine Multicentric Lymphoma

Multiple hemostatic abnormalities are associated with paraneoplastic syndrome and some malignant tumors. Lymphoma is the most common hematopoietic neoplasm in dogs, sometimes associated with hemostatic changes. The objectives of this study were to evaluate the behavior of coagulation parameters in dogs with multicentric lymphoma compared with diseased dogs without lymphoma, to separately evaluate the effect of immunophenotype (B lymphoma versus T lymphoma) on the variables of interest as well as the effect of disease stage (stage II to IV versus stage V). Specifically, a cross-sectional study was performed with a matched comparison group considering 170 dogs with B or T lymphoma (group 1) and 170 dogs with no lymphoma or other neoplastic processes but other diseases (group 0). Eight coagulation parameters were evaluated: platelet count (Plt), activated partial thromboplastin time (aPTT), prothrombin time (PT), thrombin time (TT), fibrinogen, fibrin/products of fibrinogen degradation (FDPs), fibrin D-dimers, and antithrombin (AT). Dogs with lymphoma showed prolonged PT and TT, decreased fibrinogen, increased FDP, and decreased Plt compared with group 0. The effect of disease stage was evaluated separately for dogs with stage II to IV lymphoma and dogs with stage V lymphoma; patients with stage II–IV lymphoma showed no significant differences, while in dogs with stage V lymphoma, a prolongation of PT and TT, a decrease in fibrinogen, an increase in FDPs and a decrease in Plt were found compared with the group 0. Finally, the comparison between B lymphoma and T lymphoma showed no significant differences in coagulation parameters between the two groups. Logistic regression analysis demonstrated that low fibrinogen and platelet levels were the most significant predictors of lymphoma in a cohort of canine patients. These hemostatic abnormalities in lymphoma appeared to be associated with the stage of the disease rather than the lymphoma immunophenotype. These findings pave the way for the possible scenario of lymphoma-associated fibrinolysis and the so far undescribed pattern of hyperfibrinolysis associated with the most severe stage of lymphoma.

Effects of restrictive fluid resuscitation on the clinical efficacy of treating traumatic hemorrhagic shock combined with traumatic coagulopathy

This study aims to assess the clinical efficacy of limited fluid resuscitation on traumatic hemorrhagic shock combined with traumatic coagulopathy. A cohort of 120 patients with traumatic hemorrhagic shock complicated with traumatic coagulopathy at admission were divided into two groups based on their emergency fluid resuscitation: the study group (received restrictive fluid resuscitation) and the control group (received conventional fluid resuscitation). Then, the incidence of complications, coagulation parameters, blood gas parameters and electrolyte parameters between the two groups were compared. The incidence of complications in the study group was 6.67%, which was significantly lower than the 20.00% observed in the control group (p < 0.05). Before resuscitation, there was no significant difference in coagulation parameters, blood gas parameters and electrolyte parameters between the two groups (p > 0.05), and in both groups, before and after resuscitation, the coagulation parameters after resuscitation were higher than those before resuscitation, blood gas parameters were lower than those before resuscitation, Mg2+, Cl− and Na+ levels were higher than those before resuscitation, K+ was lower than that before resuscitation, and the difference had statistical significance (p < 0.05). After resuscitation, the coagulation parameters in the study group were significantly lower than those in the control group, the BL (Blood Lactic Acid) and PaCO2 (partial pressure of carbon dioxide in arterial blood) levels in the study group were lower than those in the control group, the BE (base excess) and PaO2 levels were higher than those in the control group, and the differences were statistically significant (p < 0.05). However, after resuscitation, we found no significant difference in electrolyte parameters between both groups (p > 0.05). Restrictive fluid resuscitation was found to significantly enhance coagulation and blood gas function, stabilize water and electrolyte balance and reduce complications in traumatic hemorrhagic shock patients complicated with traumatic coagulopathy. These findings hold substantial clinical significance and merit further exploration.

Comparisons of coagulation characteristics between elderly and non-elderly patients with sepsis: A prospective study

BackgroundA blunt host defense response in older patients may contribute to different coagulation responses during sepsis. We aimed to investigate the differences in coagulation parameters between elderly and non-elderly patients with sepsis. MethodsAdult patients diagnosed with sepsis within 24 hours after admission to the intensive care unit between September 2018 and December 2020 were prospectively enrolled. Patients were categorized into the adult (18–64 years) and elderly (age ≥65 years) groups. Conventional coagulation parameters and inflammatory markers were measured on intensive care unit admission and on Days 3 and 7. Thromboelastography was performed on intensive care unit admission. The differences in the coagulation parameters between the 2 groups were evaluated. The adult and elderly patients were matched to adjust for baseline characteristics. Correlations between inflammatory markers and coagulation-related parameters were also analyzed. ResultsOf the 567 patients, 303 (53.4%) were elderly. Compared with adult patients, elderly patients had lower prothrombin time elevation, lower fibrinogen, D-dimer, and fibrin/Fib degradation product levels, and lower proportion of disseminated intravascular coagulation on intensive care unit admission; and, they had lower dynamic platelet, lower fibrinogen, and D-dimer levels during the first week in the intensive care unit. Thromboelastography parameters were generally within the normal range, although elderly patients had lower R and K values and a higher alpha angle. Comparisons of coagulation parameters between the 2 groups revealed similar results in the matched cohort. The inflammatory markers correlated with prothrombin time, activated partial thromboplastin time, and antithrombin III. ConclusionElderly patients had milder coagulation activation, accompanied by a decreased inflammatory response during sepsis, compared to non-elderly patients.

Identification of early derangements of coagulation, hematological and biochemical profiles in patients with acute pancreatitis

BackgroundAcute pancreatitis (AP) is a severe disease involving various pathological processes. We aimed to use rapid -thromboelastography (r-TEG) combined with conventional coagulation assays (CCAs) and other laboratory tests, to identify early derangements in coagulation, hematological, and biochemical profiles in patients with AP. MethodsWe enrolled 177 patients diagnosed with AP and 121 controls. Blood samples were analyzed using r-TEG, CCAs, and hematological and biochemical tests within 2 h of patient admission. All testing parameters were compared between the patients and the controls. Pearson’s correlation coefficient was used to determine the correlation between the parameters among the patients. Logistic regression analysis was performed to evaluate the effects of the variables (demographic, coagulation, hematological and biochemical) on AP. ResultsUsing r-TEG and CCAs, we observed differences in coagulation parameters between the patients with AP and the controls. The r-TEG results showed a pro-coagulant state and increased platelet activation in AP patients. Pearson’s correlation analysis showed that inflammatory indicators were strongly correlated with coagulation/platelets in the pathological process of AP. Logistic regression analysis revealed that age, K, neutrophil (NEUT), triglyceride (TG) and blood amylase (AMY) were significantly associated with the development of AP. ConclusionCoagulation profile and platelet play essential roles in the pathogenesis of AP. Pro-coagulant state and increased platelet activation in patients with AP were demonstrated using r-TEG. The r-TEG parameter K, age, NEUT, TG, and AMY may be used as potential indicators of AP.

Coagulation parameters abnormalities and their relation to clinical outcomes in hospitalized and severe COVID-19 patients: prospective study

There has been growing attention toward the predictive value of the coagulation parameters abnormalities in COVID-19. The aim of the study was to investigate the role of coagulation parameters namely Prothrombin concentration (PC), activated Partial thromboplastin Time (aPTT), D-Dimer (DD), Anti Thrombin III (ATIII) and fibrinogen (Fg) together with hematological, and biochemical parameters in predicting the severity of COVID-19 patients and estimating their relation to clinical outcomes in hospitalized and severe COVID-19 Patients. In a prospective study, a total of 267 newly diagnosed COVID-19 patients were enrolled. They were divided into two groups; hospitalized group which included 144 patients and non-hospitalized group that included 123 patients. According to severity, the patients were divided into severe group which included 71 patients and non-severe group that included 196 patients who were admitted to ward or not hospitalized. Clinical evaluation, measurement of coagulation parameters, biochemical indices, outcome and survival data were recorded. Hospitalized and severe patients were older and commonly presented with dyspnea (P ≤ 0.001). Differences in coagulation parameters were highly significant in hospitalized and severe groups in almost all parameters, same for inflammatory markers. D-dimer, AT-III and LDH showed excellent independently prediction of severity risk. With a cut-off of > 2.0 ng/L, the sensitivity and specificity of D dimer in predicting severity were 76% and 93%, respectively. Patients with coagulation abnormalities showed worse survival than those without (p = 0.002). Early assessment and dynamic monitoring of coagulation parameters may be a benchmark in the prediction of COVID-19 severity and death.

Characterization and first-in-human clinical dose-escalation safety evaluation of a next-gen human freeze-dried plasma.

BackgroundEarly plasma transfusion is life‐saving for bleeding trauma patients. Freeze‐dried plasma (FDP) provides unique formulation advantages for infusion in the prehospital setting. We describe characterization and clinical safety data of the first, next‐generation FDP stored in plastic bags with rapid reconstitution.Study design and methodsCoagulation and chemistry parameters on 155 pairs of fresh frozen plasma (FFP) and their derivative FDP units were compared. Next, a first‐in‐human, dose‐escalation safety evaluation of FDP, involving 24 healthy volunteers who donated either whole blood or apheresis plasma to create autologous FDP, was performed in three dose cohorts (270, 540, and 810 ml) and adverse events (AEs) were monitored. Cohort 3 was randomized, double‐blind with a cross‐over arm that compared FDP versus FFP using descriptive analysis for AEs, coagulation, hematology, and chemistry parameters.ResultsFDP coagulation factors, clotting times, and product quality (pH, total protein, and osmolality) post‐lyophilization were preserved. FDP infusions, of up to 810 ml per subject, were found to be safe and with no serious AEs (SAEs) related to FDP. The average time to reconstitute FDP was 67 s (range: 43–106). No differences in coagulation parameters or thrombin activation were detected in subjects infused with 810 ml of FDP compared with FFP.ConclusionThis first next‐generation FDP product preserves the potency and safety of FFP in a novel rugged, compressible, plastic container, for rapid transfusion, allowing rapid access to plasma in resuscitation protocols for therapy in acute traumatic hemorrhage.

Viscoelastic Coagulation Monitor (VCMVet) Reference Intervals and Sex Differences in Mature Adult Mice

Introduction: Viscoelastic coagulation tests are useful to assess coagulation status in the clinical setting and to aid in understanding underlying pathophysiological mechanisms that affect coagulation status. Such tests also are useful for coagulation research. Because mouse models are widely used to study molecular mechanisms in fine detail, a simple viscoelastic coagulation test requiring small blood volumes would be convenient for such studies in mice. Methods: We tested viscoelastic coagulation properties of normal healthy adult mice using a novel veterinary clinical point-of-care device, Viscoelastic Coagulation Monitor (VCM Vet™; Entegrion Corp.). Fresh whole blood was collected from 63 healthy mature adult C57 black 6N mice, with ultimately 54 mice, equal numbers of male and females, used to determine reference intervals (RIs) for VCM test parameters. Results: RIs were determined for equal numbers of male and female mice: clot time: 43.0–353.0 s; clot formation time: 49.4–137.6 s; alpha angle: 54.4–62.2°; A10: 25.0–49.6 VCM units; A20: 31.0–56.5 VCM units; maximum clot firmness: 37.6–62.8 VCM units; Lysis Index 30 (Li30): 99.8–100.0%; and Li45: 99.7–100.0%. Significant differences were found between male and female subgroups, where females had higher mean A10 and A20 and median MCF values, indicating greater clot firmness in female versus male mice. Conclusion: VCM Vet is a feasible viscoelastic coagulation test device for studies with mature adult mice, including studying inherent sex differences in coagulation parameters. Inherent differences in coagulability of male and female mice warrant further investigation to determine if such differences underlie greater coagulopathic, hemorrhagic, or thromboembolic risk during trauma or other pathophysiologic conditions.

The recombinant plant Bauhinia bauhinioides elastase inhibitor reduces rat thrombus without alterations in hemostatic parameters

The anti-inflammatory effects of the plant protease inhibitor BbCI (Bauhinia bauhinioides cruzipain inhibitor), which blocks elastase, cathepsin G, and L, and proteinase 3 has been demonstrated. Here, we investigated the recombinant rBbCI-His(6) (containing a histidine tail) in an experimental venous thrombosis model of vena cava (VC) ligature in rats, comparing to heparin. We evaluate the effects of the inhibitors (native or recombinant) or heparin on the activated partial thromboplastin time (aPTT) and prothrombin time (PT) in human and rat plasmas. The rats undergoing treatment received a saline solution or increasing concentrations of rBbCI-His(6), heparin, or a mixture of both. After 4 h of ligature VC, thrombus, if present was removed and weighed. aPTT, PT, and cytokines were measured in blood collected by cardiac puncture. aPTT, PT, and bleeding time (BT) were also measured at the time of VC (vena cava) ligature. rBbCI-His(6) (0.45 or 1.40 mg/kg) does not alter aPTT, PT or BT. No differences in coagulation parameters were detected in rBbCI-His(6) treated rats at the time of VC ligature or when the thrombus was removed. There was a significant decrease in the weight of thrombus in the animals of the groups treated with the rBbCI-His(6) (1.40 mg/kg), with the rBbCI-His(6) mixture (1.40 mg/kg) + heparin (50 IU/kg) and heparin (100 IU/kg) in relation to control group (saline). The growth-related oncogene/keratinocyte chemoattractant (GRO/KC) serum levels in rats treated with rBbCI-His(6) (1.40 mg/kg) or heparin (200 IU/kg) were reduced. In the experimental model used, rBbCI-His(6) alone had an antithrombotic effect, not altering blood clotting or bleeding time.

Prospective Study Reveals Increased Platelet Function Associated with Multiple Myeloma and Its Treatment

Background: Multiple Myeloma (MM) is a rare incurable bone marrow cancer characterised by a malignant proliferation of plasma cells. MM is usually preceded by a premalignant and benign Monoclonal Gammopathy of Undetermined Significance (MGUS). The incidence of arterial and venous thrombosis in MM is substantially higher than in the normal population, however the cause of this increased thrombosis risk and the impact of MM on platelet function is unclear. Treatments for both newly diagnosed and relapsed/refractory patients with MM include Immunomodulatory drugs (IMiDs) such as thalidomide/lenalidomide-based combinations. These treatments improve considerably patient outcomes, however iMiD treatment also increases the risk of thrombotic complications in these patients. Aims: In this prospective study we explored the impact of MM and its treatment on platelet function. Methods: High throughput functional analysis was performed using platelets from normal healthy controls (n=31) and patients with MGUS (n=18), smouldering multiple myeloma (SMM, n= 20), and MM (26). The MM group was further divided into 3 treatment cohorts; (1) no treatment, (2) treatment with proteasome inhibitor (PI) and dexamethasone (Dex), and (3) treatment with PI, Dex, immunomodulatory drug (iMiD) and direct oral anticoagulant. Platelet aggregation and activation (fibrinogen binding and P-selectin exposure) were measured in response to a concentration range of agonists including ADP, the thrombin receptor agonist TRAP-6, collagen, collagen-related peptide (CRP), a thromboxane receptor agonist U46619 and epinephrine. Cereblon protein was detected in platelet protein extracts by immunoblot analysis. Results: Consistent with previous reports, modestly increased VWF and factor VIII levels were detected in MM patients, but no additional differences in coagulation parameters were detected in patient groups compared to normal healthy controls (other than expected due to anticoagulant usage). Platelet aggregation in response to each agonist was increased significantly in the MM patient group compared to the normal healthy controls, suggesting that platelet reactivity is elevated in MM patients through a common mechanism that is shared by different activation pathways or the involvement of multiple mechanisms. P-selectin exposure on platelets from MM patients was not significantly different from normal healthy donors, indicating that enhanced platelet reactivity in MM is specifically through modulation of integrin αIIbβ3 activation, fibrinogen binding and therefore enhanced aggregation. The effects of treatment on platelet function in patients on iMiD vs. non iMiD treatment were assessed. In the iMiD treatment group, patient platelets aggregated in response to lower concentrations of ADP, collagen, epinephrine and CRP in samples taken post-treatment compared to those taken before and during treatment. This demonstrates an increased sensitivity to platelet activation in these patients induced by treatment. Immunoblot analysis revealed that platelets contain cereblon, a therapeutic target of lenalidomide. The potential direct effects of iMiDs on platelets in vitro was therefore explored. Lenalidomide treatment (10mM) increased the ability of platelets to aggregate in response to low concentrations of each agonist tested when compared to normal controls. Conclusions: Platelet reactivity is increased in multiple myeloma and increased further upon iMiD treatment. The presence of the key therapeutic target for iMiDs in platelets and the ability of lenalidomide to modulate platelet function directly, reveals new avenues for investigation to determine the underlying mechanism of action. Disclosures Laffan: CSL: Consultancy; Pfizer: Consultancy; Sobi: Consultancy; Roche: Consultancy; LFB: Consultancy; Shire: Consultancy; Octapharma: Consultancy; Bayer: Speakers Bureau; Roche-Chugai: Speakers Bureau; Takeda: Speakers Bureau; Leo-Pharma: Speakers Bureau; Pfizer: Speakers Bureau. Shapiro:Bayer: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; NovoNordisk: Consultancy, Speakers Bureau; Sobi: Consultancy, Speakers Bureau; Chugai/Roche: Consultancy, Speakers Bureau; Shire/Takeda: Consultancy, Speakers Bureau. Thakurta:Oxford University: Other: visiting professor; Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Ramasamy:Takeda: Research Funding; Janssen: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Research Funding; Amgen: Research Funding; Amgen: Honoraria; Takeda: Honoraria; Sanofi: Honoraria; Oncopeptides: Honoraria; Takeda: Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; Bristol Myers Squibb: Honoraria; Janssen: Membership on an entity's Board of Directors or advisory committees; Bristol Myers squibb: Membership on an entity's Board of Directors or advisory committees. Gibbins:Bristol Myers Squibb: Research Funding; Arena Pharmaceuticals: Research Funding.

Coagulation in the HIV-positive pregnant patient : a thromboelastography study

Background: HIV infection is associated with haematological changes, including thrombocytopaenia. Pregnancy induces a hypercoagulable state. There are limited data on the coagulation status of women with term pregnancy and HIV receiving antiretroviral medication. Regional anaesthesia is the technique of choice for caesarean section (CS), and is contraindicated in a hypocoagulable state. We therefore investigated the coagulation status of term pregnant women with HIV, presenting for elective CS. Methods: This was a single-centre cross-sectional observational study, using thromboelastography, comparing the coagulation status of HIV-negative and -positive women with no other comorbidities, in pregnancy at term. A blood sample was taken immediately prior to spinal anaesthesia, and thromboelastography was performed within four minutes. In addition, platelet count, haemoglobin, and fibrinogen level were measured. Results: Blood samples were obtained from 75 patients. There were no between-group differences in obstetric and demographic data, and no difference in platelet count. The mean (standard deviation [SD]) fibrinogen level was higher in HIV positive women (3.9 [1.5] vs 3.5 [0.7] g/L) respectively, p = 0.04. There were no significant differences in the r time, alpha angle, k time, maximum amplitude (MA), or LY-30. Conclusions: The results of this thromboelastography study show that in asymptomatic HIV-positive pregnant patients on antiretroviral treatment, there are no significant differences in coagulation parameters when compared with HIV-negative patients. This suggests that routine assessment of coagulation is unnecessary before spinal anaesthesia in patients without further comorbidities. Further studies could demonstrate the incidence of abnormalities in coagulation or platelet function in patients with AIDS-defining disease or HIV-positive patients with other comorbidities.

French lyophilized plasma versus fresh frozen plasma for the initial management of trauma‐induced coagulopathy: a randomized open‐label trial

Background Guidelines recommend beginning hemostatic resuscitation immediately in trauma patients. We aimed to investigate if French lyophilized plasma (FLyP) was more effective than fresh frozen plasma (FFP) for the initial management of trauma-induced coagulopathy. Methods In an open-label, phase 3, randomized trial (NCT02750150), we enrolled adult trauma patients requiring an emergency pack of 4 plasma units within 6h of injury. We randomly assigned patients to receive 4-FLyP units or 4-FFP units. The primary endpoint was fibrinogen concentration at 45min after randomization. Secondary outcomes included time to transfusion, changes in hemostatic parameters at different time-points, blood product requirements and 30-day in-hospital mortality. Results Forty-eight patients were randomized (FLyP, n=24; FFP, n=24). FLyP reduced the time from randomization to transfusion of first plasma unit compared with FFP (median[IQR],14[5-30] vs. 77[64-90]min). FLyP achieved a higher fibrinogen concentration 45min after randomization compared with FFP (baseline-adjusted mean difference, 0.29gL-1 ; 95% confidence interval [CI], 0.08-0.49) and a greater improvement in prothrombin time ratio, factor V and factor II. The between-group differences in coagulation parameters remained significant at 6h. FLyP reduced fibrinogen concentrate requirements. Thirty-day in-hospital mortality rate was 22% with FLyP and 29% with FFP. Conclusion FLyP led to a more rapid, pronounced and extended increase in fibrinogen concentrations and coagulopathy improvement compared with FFP in the initial management of trauma patients. FLyP represents an attractive option for trauma management, especially when facing logistical issues such as combat casualties or mass casualties related to terror attacks or disasters.

Coagulology, biochemical profile and muscle pathology in calves diagnosed with nutritional muscular dystrophy.

The aim of this study was to explain the correlations between selenium deficiency, hemostatic and biochemical disorders, and the progression of pathological changes in calves diagnosed with nutritional muscular dystrophy (NMD). The study was performed on 20 calves with supplementation of 8 ml selenium and vitamin E preparation and 20 calves with symptoms of NMD. Blood was sampled from calves aged 5, 12 and 19 days. On day 19, samples of the biceps femoris muscle were collected from 6 animals in each group for histopathological analysis. The following blood parameters were determined: PLT, PT, TT, APTT, fibrinogen and D-dimer concentrations, antithrombin III activity, glucose, selenium and vitamin E concentrations, activity of CK, LDH and GSH-Px. Muscle sections were stained with H&E and HBFP. Platelet counts were significantly lower in calves with symptoms of NMD. No significant differences in coagulation parameters were observed between the groups. Sick calves were diagnosed with hyperglycemia and elevation of CK and LDH activity. Selenium and vitamin E concentrations in the blood serum were significantly lower in the experimental group together with significant drop in GSH-Px activity. Changes characteristic of Zenker's necrosis were observed in a muscle of the sick animals. To our best knowledge this is the first study in which the attempt was made to explain the relationship between selenium deficiency and changes in the coagulation system in ruminants.

Rapid dry plasma thawing system: An alternative to conventional thawing baths.

BACKGROUND:Fresh frozen plasma (FFP) should be thawed before transfusing to the patient. Prolonged or uncontrolled thawing can denature plasma proteins. The potential risk of contamination by wet thawing had always been a point of concern.AIMS:Here, we compared and evaluated the effect of thawing on clotting factor activities by two different methods (wet and dry) and other factors such as risk of bacterial contamination, throughput, turnaround time, and efficacy of thawing.SUBJECTS AND METHODS:All FFPs were prepared from Group O donors and stored at −40°C. Twenty-one FFPs were thawed in Plasmatherm II at 45°C for 15 min and another 21 were thawed in thawing bath at 37°C for 20–30 min randomly. Analysis of prothrombin time, activated partial thromboplastin time, fibrinogen, and factor VIII was done in ACL TOP 300 (IL) at the time of preparation and immediately after thawing of FFPs. Volume, duration of thawing, ease of use, accessibility, and equipment maintenance were also compared.RESULTS:There was a statistically significant difference in coagulation parameters after thawing in both methods compared to the time of preparation (P < 0.05), but all values were within normal limits. There was no significant difference in coagulation parameters between the two methods (P > 0.05). Mixed bacterial growth was observed from swabs taken from the water bath.CONCLUSION:Plasmatherm II can be a good alternative to water bath to rapidly thaw FFPs by preserving coagulation factors and eliminating the risk of bacterial contamination.

Citrate versus Acetate-Based Dialysate in On-Line Haemodiafiltration. A Prospective Cross-Over Study

Background and Aims: A bicarbonate dialysate acidified with citrate (CD) has been reported to have local anticoagulant effect and improves biocompatibility. This study examines the effect of CD on dialysis efficiency, coagulation, acid-base status, electrolytes, and inflammation in patients in on-line hemodiafiltration (OL-HDF). Methods: 35 patients in OL-HDF were enrolled in a prospective, cross-over study for a 24-week period and two phases alternating CD and acetate dialysate fluid (AD). Parameters on study were predialysis levels of bicarbonate and ionic calcium, reactive C Protein (CRP), and beta-2 microglobulin (B2MG) and postdialysis levels of activated tromboplastine time, bicarbonate, and ionized calcium. Results: No significant differences in coagulation parameters, pH, and predialysis bicarbonate were found. The postdialysis bicarbonate and postdialysis calcium were lower with CD. Dialysis efficiency was greater with CD. Regarding inflammatory parameters, both CRP and B2MG were lower using CD. Conclusion: The use of CD is safe and effective in OL-HDF, and it improves dialysis efficacy, postdialysis alkalosis, and inflammation.

Hemorrhage requiring surgical intervention among children on pulsatile ventricular assist device support

Bleeding complications are a source of morbidity after Berlin EXCOR VAD implantation yet remain poorly characterized. We evaluated our experience to describe the bleeding complications among pediatric VAD recipients. We hypothesized that those with bleeding requiring exploration had abnormal coagulation profile compared with those without bleeding. The retrospective study included 43 consecutive patients with end-stage heart failure supported on pediatric mechanical cardiac support as a bridge to transplantation. Day-/event-based analysis on factors below associated with (i) bleeding and (ii) bleeding in next 48h. Cases with bleeding were compared with day-matched patients without bleeding complications. Among 43 subjects bleeding occurred in 47% of cases, which necessitated exploration or chest tube placement. Twenty of 34 interventions for bleeding occurred in the first seven post-operative days. No differences in coagulation parameters or use of antiplatelet agents were noted among those who had bleeding vs. those who did not. Our results indicate that (i) re-bleeding requiring re-exploration was common, (ii) most of the bleeding occurred early post-implantation, (iii) there were no differences in coagulation parameters or the use of antiplatelet agents within 48h of bleeding compared with those who did not bleed on each successive post-operative day.

Resuscitation With Different Volume Expanders Does Not Influence Coagulation After Antidoting Dabigatran With Its Specific Fab In a Pig Model Of Hemorrhagic Shock

IntroductionA specific antibody fragment (Fab) is currently in development to reverse the effects of dabigatran in cases of life-threatening bleeding or emergency surgery. In trauma, different volume expanders are used for resuscitation to compensate for blood loss and hemorrhagic shock. The influence of volume expanders on binding of dabigatran to the Fab, however, is not known. Therefore, in this study we investigated whether frequently used infusion solutions affect binding of dabigatran to the Fab antidote and the resulting effects on coagulation assays. MethodsAll studies were performed after ethical approval. Dabigatran etexilate was given to pigs for 3 days (30 mg/kg bid) and on day 4 a 90 min infusion of dabigatran (30 min:0.77mg/kg/h; 60 min:0.26 mg/kg/min) was performed in anesthetized pigs. Then ∼50% (100 mL/min) of total blood volume was removed and animals were randomized to (n=5/group): balanced Ringer's solution, 6% HES 130/0.4, 6% HES 200/0.5, 4% gelatin, retransfusion of washed red blood cells (RBCs) or control (no haemodilution). Resuscitation consisted of, 1:1 to blood loss for crystalloids, 25 mL/kg for colloids, and 12 mL/kg for RBC. Antidote was then given (30 mg/kg iv) and serial blood samples were taken for up to 24 hrs to measure active dabigatran as diluted TT (Hemoclot) and total dabigatran (LC-MS/MS). Coagulation was assessed by means of aPTT, diluted PT (dPT, Neoplastin R, 1:100), i-Stat ACT celite (ACT), and ROTEM, ExTem and InTem reagents. Data expressed as mean ± SE and analyzed with ANOVA. ResultsHemodilution resulted in a substantial reduction of hemostatic parameters (Hemoglobin, platelets and leukocytes) with all agents, except after RBC transfusion vs control. Mean plasma dabigatran levels measured at dTT were 640 ± 60 ng/mL after infusion and 625 ± 123 ng/mL after hemodilution without significant differences between groups. Administration of 30 mg/kg iv Fab resulted in a comparable reduction of active dabigatran in all groups, with a calculated half-life of 3.2 ± 0.1 hrs. The best correlation between dTT and other coagulation assays was obtained for the dPT (r2=0.6321), the ACT-celite (r2=0.6605) and clotting time from ExTEM and InTEM ROTEM (r2=0.5169 and 0.7303, respectively). The correlation between aPTT and dTT was moderate: r2=0.2321. Overall, coagulation was prolonged upon dabigatran treatment as indicated by the dPT (from 32.3±10.6 to 162.7±18.1 sec), aPTT (fom 44.6±6.2 to 67.9±10.3 sec), ACT (from 97±6 to 297±25 sec), CT ExTem (from 36.5±3.7 to 1205.4±598.3 sec) and CT InTem (from 122.0±11.9 to 989.3±218.9 sec). Fab treatment restored coagulation by on average 73% (between 58 and 95%, depending on the applied assay) at 5 minutes following administration. The dPT shortened to 43.8±24.1 sec, the aPTT to 30.6±5.5 sec, the ACT to 126±25 sec, the CT ExTem to 124.3±83.4 sec, and the CT InTem to 300.7±168.7 sec, with no significant differences in coagulation parameters between the various volume expanders. However, resuscitation with 4% gelatin and Fab treatment resulted in a significant lesser reduction of the CT InTem compared to the other volume expanders: 631.6±360.4 sec for 4% gelatin and 203.8±22.4, 251.7±157.2, and 280.8±235.3 sec for 6% HES 200/0.5, 6% HES 130/0.4, and Ringers, respectively. All coagulation parameters were comparable between the various volumes expanders from 60 minutes onward. Twenty four hours after Fab administration all coagulation parameters were almost back to baseline values with 26.9±62.8 ng/mL dabigatran, 50.9±12.6 sec for the dPT, 48.6±13.5 sec for the aPTT, 121±6 sec for ACT, 50.0±3.4 sec for CT ExTem, and 189.7±24.5 sec for CT InTem. ConclusionsClinically used infusion solutions for volume resuscitation do not interfere with binding of dabigatran to its specific antidote. Inhibition of dabigatran with its specific Fab antidote at this particular dose, restored coagulation by almost 70% This effect was independent of the volume applied for resuscitation. Disclosures:Spronk:Boehringer Ingelheim Pharma GmbH & Co. KG: Research Funding. van Ryn:Boehringer Ingelheim Pharma GmbH & Co. KG: Employment. Grottke:Boehringer Ingelheim Pharma GmbH & Co. KG: Research Funding.

Heparin/N-acetylcysteine: An adjuvant in the management of burn inhalation injury: A study of different doses

PurposeNebulized heparin may reduce fibrin cast formation and reduce the degree of airway obstruction in burn inhalation injury. MethodsTwenty-nine patients admitted to burn intensive care unit (ICU) within 24 hours of burn inhalation injury were included in this prospective double-blinded randomized study. Group H5 received nebulized heparin sulfate 5,000 IU, and group H10 received nebulized heparin sulfate 10,000 IU. Heparin was given in alternation with N-acetylcysteine every 2 hours. Lung injury score assessed daily for 7 days was the primary outcome. Duration of mechanical ventilation, coagulation profile, length of ICU stay, and mortality were the secondary outcomes. ResultsMedian lung injury scores were significantly lower in group H10 on days 5 (1.9 vs 1), 6 (1.4 vs 0.5), and 7 (1.3 vs 0.5). Group H10 had also a lower duration of mechanical ventilation than did group H5 (P = .037). The groups had no significant difference in coagulation parameters, length of ICU stay (P = .17), and mortality (P = .6). ConclusionsNebulized heparin 10,000 IU decreased lung injury scores and duration of mechanical ventilation but had no effect on length of ICU stay and mortality. Moreover, nebulized heparin 10,000 IU was safe and had no effect on coagulation parameters.

Increased expression levels of vitronectin in the maternal-fetal interface of placenta in early-onset severe preeclampsia

Preeclampsia(PE) is a pregnancy-specific disease, the pathogenesis of which remains unclear. The present study was designed to analyze whether vitronectin(VN), a multifunctional human glycoprotein, is expressed in PE and normal placentas. Furthermore, we aimed to explore VN expression profiles in relation to the pathogenesis of PE. Placental samples and plasma of early-onset severe PE (EOSP), late-onset severe PE (LOSP) and 2control groups corresponding to EOSP and LOSP were collected. Immunohistochemistry, immunofluorescence and western blot analysis were used to detect VN protein expression profiles. mRNA expression levels of VN were detected by reverse transcription polymerase chain reaction (RT-PCR). The impact of VN on coagulation was investigated by comparing differences in coagulation parameters. Our results demonstrate that expression levels of VN in the maternal-fetal interface of the EOSP group are the highest (P<0.001). The expression levels of VN in descending order in infarct center, infarct edge, near infarct tissues and away from infarct tissues were identified (P<0.001). Immunofluorescence and immunoblotting were consistent with immunohistochemical results. The VN mRNA expression was detected. Prothrombin time (PT) was significantly shorter in EOSP compared with the control group (P<0.05), which had a significant negative correlation with expression levels of VN in the placental tissue of the group. VN may play a key role in repairing the lesions and limiting necrotic components into maternal blood through its adhesion. VN may be involved in the pathogenesis of EOSP by inducing an imbalance between coagulation and fibrinolysis.

Evaluation of coagulation status in dogs with naturally occurring canine hyperadrenocorticism

To determine whether or not there are differences in coagulation parameters (eg, thrombelastography [TEG], activated partial thromboplastin time [aPTT], prothrombin time [PT], and fibrinogen) among dogs with naturally occurring hyperadrenocorticism (HAC), dogs with HAC undergoing medical management, and dogs without HAC. Prospective, observational study. Veterinary teaching hospital. Forty-six client-owned dogs undergoing adrenal function testing. None. Nine dogs were diagnosed with HAC de novo, 19 dogs were presented for therapeutic monitoring of previously diagnosed HAC, and 18 dogs did not have HAC. Variables compared between groups were age, body weight, platelet count, mean platelet volume, serum concentrations of cholesterol, triglycerides, antithrombin, PT, aPTT, fibrinogen, and TEG parameters (eg, alpha angle, R, K, and maximum amplitude [MA]). Dogs with HAC and dogs treated for HAC had higher serum cholesterol than dogs without HAC (P < 0.05). All groups had mean MA greater than the institutional reference interval. There was a weak, positive correlation between hematocrit and MA that was independent of diagnosis (r(2) = 0.266, P = 0.004). The results of this study do not support the supposition that a significant difference exists in coagulation tendencies between dogs with HAC prior to treatment, dogs with HAC during treatment, and dogs without HAC. This disagreement with the classically accepted notion that HAC leads to a hypercoagulable state could be due to a couple of possibilities. Namely, the link between HAC and hypercoagulability may be relatively weak, or our findings may be the result of a type II error either as a result of a small sample size or the use of coagulation assays that are insensitive to the effects of HAC on the hemostatic system.

Elevated Cardiac Troponin I in Sepsis and Septic Shock: No Evidence for Thrombus Associated Myocardial Necrosis

BackgroundElevated cardiac troponin I (cTnI) is frequently observed in patients with severe sepsis and septic shock. However, the mechanisms underlying cTnI release in these patients are still unknown. To date no data regarding coagulation disturbances as a possible mechanism for cTnI release during sepsis are available.Methodology/Principal FindingsConsecutive patients with systemic inflammatory response syndrome (SIRS), sepsis or septic shock without evidence of an acute coronary syndrome were analyzed. Coagulation parameters (clotting time (CT), clot formation time (CFT), maximum clot firmness (MCF), α-angle) were assessed in native whole blood samples, and using specific activators to evaluate the extrinsic and intrinsic as well as the fibrin component of the coagulation pathway with the use of rotational thrombelastometry (ROTEM).Thirty-eight patients were included and 22 (58%) were cTnI-positive. Baseline characteristics between TnI-positive and -negative patients were similar. The CT, CFT, MCF and the α-angle were similar between the groups with trends towards shorter CT in the extrinsic and fibrin activation.Conclusions/SignificanceWe found no differences in coagulation parameters analyzed with rotational thrombelastometry between cTnI-positive and -negative patients with SIRS, severe sepsis, and septic shock. These findings suggest that pathophysiological mechanisms other than thrombus-associated myocardial damage might play a major role, including reversible myocardial membrane leakage and/or cytokine mediated apoptosis in these patients.